Treatment of people with acute HCV infection
Acute HCV infection refers to the 6-month period after infection acquisition, though definitions vary111 and the distinction between acute and early chronic infection is somewhat arbitrary. In Australia, it is estimated that approximately 8500–9000 new infections occur each year.1,3 While in some cases acute HCV infection may develop after discrete exposure (eg, a needle-stick injury in a health care worker), detection of acute HCV infection is often hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV, including PWID. Another high-risk group for HCV transmission is HIV-positive MSM, in whom sexual or permucosal transmission has become increasingly common.93,112,113 Risk factors for sexual transmission include, but are not limited to, traumatic sexual practices, recreational non-injecting drug use, group sex and the presence of a co-existent sexually transmitted infection.114
Acute HCV infection is characterised by the appearance of HCV RNA in blood within 2–14 days of exposure, elevation of liver-associated enzyme levels (particularly ALT), and development of HCV antibodies within 30–60 days of exposure. Up to 80% of acute HCV infections are asymptomatic, making detection and estimation of duration of infection difficult if seroconversion cannot be documented. Clinical features suggestive of acute infection include significant elevation of ALT level or an acute illness manifest by jaundice. However, only 15%–30% of those infected develop a symptomatic illness, and elevation of ALT level is non-specific. Acute infection should be suspected if the clinical signs and symptoms are compatible with acute hepatitis C — such as serum ALT level > 10 x ULN and jaundice in the absence of a history of chronic liver disease or other causes of acute hepatitis, and/or if a likely recent source of transmission is identifiable. The preferred criteria for diagnosis of acute HCV infection are: i) positive anti-HCV IgG and a documented negative anti-HCV IgG in the previous 12 months; or ii) positive serum HCV RNA test and a documented negative serum HCV RNA test and negative anti-HCV IgG in the previous 12 months. Alternative, less stringent criteria are the presence of positive serum HCV RNA regardless of anti-HCV IgG and with: i) an acute rise in ALT level > 10 x ULN; or ii) an acute rise in ALT level > 5 x ULN, with documented normal ALT level within the past 12 months; or iii) in individuals with a previously high ALT level, an acute rise to 3.5 times the baseline ALT level; and in the absence of serological evidence of HAV or HBV infection or other causes of acute hepatitis. Documentation of seroconversion is difficult in the absence of routine serological testing, but monitoring of at-risk populations, including PWID115 and HIV-positive MSM, may be beneficial. There is no single definitive laboratory test to distinguish acute from chronic HCV infection.
Monitoring during acute infection
Individuals presenting with acute HCV infection should be monitored using HCV RNA, transaminase (ALT, AST) levels, bilirubin level and INR every 2–6 weeks for the first 6 months or until parameters have stabilised and spontaneous clearance has either occurred or is deemed unlikely.116 Management is predominantly supportive, and admission to hospital is rarely required unless symptoms are uncontrolled or there is concern about rising bilirubin levels and/or INR. Acute liver failure is rare (< 1%) but may be indicated by a rising INR. Any person with an INR > 1.5 or signs of acute liver failure should be referred urgently to a liver transplant centre. Paracetamol and alcohol should be avoided during the period of acute HCV infection. Antiviral treatment during acute liver failure following HCV infection should only be considered by experienced clinicians and in conjunction with a liver transplant specialist..
Spontaneous clearance after acute HCV infection occurs in 20%–25% of individuals.117 Predictors of spontaneous clearance include jaundice, elevated ALT level, female sex, younger age and host genetic polymorphisms (including IFNL3), although none of these factors can be used to predict clearance at the individual level. In most cases, clearance occurs within the first 6 months after infection, although late clearance has been demonstrated in a small proportion of individuals.118 Fluctuating viraemia is common in the first few months after infection, with variable patterns.119 A single HCV RNA test result below the limit of detection should not be taken as an indication of clearance; at least two undetectable HCV RNA test results, a minimum of 1 month apart, are required before clearance can be confirmed. Conversely, indicators of likely chronicity include a failure of reduction in HCV viral load of > 1 log10 IU/mL at 4 weeks, or a detectable HCV RNA test result at 12 weeks after initial presentation.120
Treatment of acute HCV infection
The optimal timing and regimen for acute hepatitis C treatment is currently unclear due to a lack of data with IFN-free DAA therapies. In the setting of IFN-based therapy, acute HCV infection can be treated with shorter and simpler therapeutic regimens, to give a similar or even greater SVR than in chronic HCV infection.121 This paradigm is unproven in the setting of IFN-free DAA therapies and is currently the subject of ongoing research studies. If spontaneous clearance has not occurred by 6 months after presentation, the person can be considered to have chronic HCV infection and treated according to current DAA treatment guidelines. Treatment can be considered earlier in specific situations, including occupationally infected health care workers. Further, there may be a population-level benefit from treating early to prevent ongoing transmission events, particularly in communities such as HIV-positive MSM. In the situation where a decision has been made to commence therapy early, within the first 6 months after infection, it is still recommended to hold treatment by monitoring HCV RNA for 12–16 weeks to determine that spontaneous clearance is unlikely. If treatment with DAA-based therapy is considered in the first 6 months after HCV infection, a standard duration of 8–12 weeks should be applied, or the patient entered into a research study pending further data (note that the PBS criteria for treatment specify chronicity as a criterion for eligibility). There is no place for the use of post-exposure prophylaxis with antiviral therapy after HCV exposure. Following acute HCV infection, all individuals should undergo risk behaviour education and discussion regarding the possibility of reinfection risk after spontaneous or treatment-induced clearance.